Abstract Obesity is associated with the overall risk of certain cancers, including breast cancer. The prevailing view is that metabolic alterations associated with obesity result in the production of excess vascular endothelial growth factor (VEGF) thereby establishing a local and systemic environment that favors the development and progression of breast cancer. We need to understand how VEGF from adipose is integrated with mammary tumor growth and vascular activity to modulate tumor progression. The MMTV-PyMT mouse is a clinically-relevant model for studying breast cancer progression as mammary tumors grow spontaneously over time; however, little is known about the distribution of VEGF between various organs. We sought to compare the basal VEGF protein expression in skeletal muscle, adipose tissue and mammary tumors from MMTV-PyMT mice and compared these levels against background nontransgenic FVB/N mice. Normal expression of VEGF protein was 69.4 ± 2.1 pg/mL in skeletal muscle and 59.0 ± 7.3 pg/mL in adipose tissue of wild-type (FVB background) control mice. The average expression level of VEGF protein in mammary tumors of MMTV-PyMT mice was 61.8 ± 31.3 pg/mL. Adipose tissue of MMTV-PyMT exhibited 324% greater (191.2 ± 37.6 pg/mL, p<0.01) VEGF protein expression compared to adipose tissue of control FVB mice, and 309% greater (p<0.05) VEGF protein compared to tumor VEGF expression. These data imply that stromal expression of VEGF may be a critical determinant regulating the angiogenic phenotype in breast cancer, and further suggests that cross-talk between the stromal environment and tumor is likely to be essential in promoting tumor growth and progression. NIH 5T32-HL090610, AHA 10BGIA3630002, ACS 116837IRG0906101 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3269. doi:1538-7445.AM2012-3269